Pharmacokinetics and predicted neutralization coverage of VRC01 in HIV-uninfected participants of the Antibody Mediated Prevention (AMP) trials

Summary The phase 2b AMP trials are testing whether the broadly neutralizing antibody VRC01 prevents HIV-1 infection in two cohorts: women in sub-Saharan Africa, and men and transgender persons who have sex with men (MSM/TG) in the Americas and Switzerland. We used nonlinear mixed effects modeling of longitudinal serum VRC01 concentrations to characterize pharmacokinetics and predict HIV-1 neutralization coverage. We found that body weight significantly influenced clearance, and that the mean peripheral volume of distribution, steady state volume of distribution, elimination half-life, and accumulation ratio were significantly higher in MSM/TG than in women. Neutralization coverage was predicted to be higher in the first (versus second) half of a given 8-week infusion interval, and appeared to be higher in MSM/TG than in women overall. Study cohort differences in pharmacokinetics and neutralization coverage provide insights for interpreting the AMP results and for investigating how VRC01 concentration and neutralization correlate with HIV incidence.